Transcriptomic characterization revealed that METTL7A inhibits melanoma progression via the p53 signaling pathway and immunomodulatory pathway

PeerJ

article

Duoli Zhang¹  Tao Zou¹  Qingsong Liu²  Jie Chen¹  Mintao Xiao¹  Anfu Zheng¹  Zhuo Zhang¹  Fukuan Du¹  Yalan Dai⁵  Shixin Xiang⁶  Xu Wu¹  Mingxing Li¹  Yu Chen¹  Yueshui Zhao¹  Jing Shen¹  Guiquan Chen⁷  Zhangang Xiao¹ 

[1] Department of Pharmacology, School of Pharmacy, Southwest Medical University, Laboratory of Molecular Pharmacology;Department of Pathology, The First People’s Hospital of Neijiang;Cell Therapy & Cell Drugs of Luzhou Key Laboratory;South Sichuan Institute of Translational Medicine;Department of Oncology, Affiliated Hospital of Southwest Medical University;Department of Pharmacy, University-Town Hospital of Chongqing Medical University;Chinese Medicine Hospital Affiliated to Southwest Medical University

关键词: p53 signaling pathway;    METTL7A;    Melanoma;    Immunomodulation;   

DOI  :  10.7717/peerj.15799

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

METTL7A is a protein-coding gene expected to be associated with methylation, and its expression disorder is associated with a range of diseases. However, few research have been carried out to explore the relationship between METTL7A and tumor malignant phenotype as well as the involvement potential mechanism. We conducted our research via a combination of silico analysis and molecular biology techniques to investigate the biological function of METTL7A in the progression of cancer. Gene expression and clinical information were extracted from the TCGA database to explore expression variation and prognostic value of METTL7A. In vitro, CCK8, transwell, wound healing and colony formation assays were conducted to explore the biological functions of METT7A in cancer cell. GSEA was performed to explore the signaling pathway involved in METTL7A and validated via western blotting. In conclusion, METTL7A was downregulated in most cancer tissues and its low expression was associated with shorter overall survival. In melanoma, METTL7A downregulation was associated with poorer clinical staging, lower levels of TIL infiltration, higher IC50 levels of chemotherapeutic agents, and poorer immunotherapy outcomes. QPCR results confirm that METTL7A is down-regulated in melanoma cells. Cell function assays showed that METTL7A knockdown promoted proliferation, invasion, migration and clone formation of melanoma cells. Mechanistic studies showed that METTL7A inhibits tumorigenicity through the p53 signaling pathway. Meanwhile, METTL7A is also a potential immune regulatory factor.

【 授权许可】

CC BY